DESCRIPTION: (Applicant's Description) The goal of this program is to develop a daily trans-mucosal drug product for premenopausal women consisting of the gonadotropin-releasing hormone agonist deslorelin (D), with partial replacement of estradiol (E2) and testosterone (T). The low dose of add-back E2 gives serum levels of estrogen lower than at any time in the menstrual cycle. The add-back dose of T is calculated to just replace the ovarian T production blocked by the action of the GnRHA. The hormonal drug product is designed for the long-term treatment of women at high risk of breast cancer with a BRCA1 mutation. The long-term aim is to achieve (and demonstrate by randomized trial) substantially reduced breast cancer risk in these women, and to enhance (and demonstrate by randomized trial) the efficacy of premenopausal mammographic screening in these women by reducing their mammographic densities and hence improving the sensitivity and specificity of premenopausal mammography. The scientific basis of the hypothesized reduction in breast cancer risk includes the known reduction in breast cancer risk associated with the reduced sex-steroid levels after oophorectomy. These reduced sex-steroid levels lead to lower mitotic activity in breast epithelium. Reduction of such epithelial mitotic activity in the endometrium induced by oral contraceptives has been repeatedly demonstrated to lead to very significant long-term reduction in the risk of endometrial cancer. This demonstrates that reducing the relevant cell proliferation may produce profound reductions in risk. An early sign of reduced breast cell proliferation should be a reduction in mammographic densities. And, the first specific aim of the study is to demonstrate the reduction of mammographic densities with our current intranasal drug product. The second specific aim is to demonstrate that the add-back E2 plus T prevents signs and symptoms of hypoestrogenism. This 12-month study is designed to develop a 25 subject experience to confirm trial methodology, including the reduction of mammographic densities. This will be a multi-center single dose-level study. Mammographic densities will be quantitated at baseline, after 6 and 12 months of treatment and after 12 months off study. Controls will be of similar age, family history of breast cancer and BRCA1 mutations. Mammographic density measurements will be made in a masked objective manner and such non-randomized controls should, therefore, be adequate for establishing the statistical significance of any regimen-induced reduced mammographic densities, the primary aim of this study.